1. Field of the Invention
The present invention relates to a cell penetrating peptide produced by oxidative modification. In particular, it relates to a cell penetrating peptide dimer having disulfide linkage. This dimer improves past characteristics of the cell penetrating peptide, and especially for improving the problem of drug stability when applied in drug carriers.
2. Description of the Related Art
One major problem in chemotherapy of cancer treatment is non-selective toxicity, which causes undesirable side effects, a narrow therapeutic window and a compromised clinical prognosis, because drugs do not identify differences between normal cells and cancer cells. In order to reduce damages to normal tissues, sub-optimal doses are often administered for anticancer chemotherapeutics, but the desired effects cannot be achieved. For circumventing those challenges, targeted drug delivery systems hold significant promise to improve drug efficacy and lower side effects by enabling the drug to a specific cell type. To date, many researches show that monoclonal antibodies, peptides, proteins, and small molecules have been used to selectively bring drugs to cancer cells with upregulated receptors by forming carrier-drug conjugates. However, none of the carrier-drug conjugates produced by peptides has successfully launched. This may be due to several reasons including (a) the difficulty in discovering the appropriate ligand matched for the targeted receptors on the cell surface; (b) the lack of information on the mechanisms of uptake and elimination of the ligand inside the cells, and (c) the limited number of systematic studies on the relationships between the physicochemical and transport properties of the conjugates.
Recently, the discovery of a new cell penetrating peptide (CPP) may contribute some ideas to solve those problems mentioned above. This peptide, CPPecp, derived from the region of human eosinophil cationic protein [ECP(32-41)]. It has previously been proven that the motif located within the CPPecp shows heparin or heparan sulfate binding activity and the CPPecp exhibits low cell toxicity, moderate migration inhibition to cancer cell, and highly cell-penetrating efficacy through macropinocytosis. Such functional characteristics of CPPecp have brought itself to the claim to be a drug carrier for medication.
However, in general, natural peptides tend to have relatively short circulating plasma half-lives, low permeability and metabolic instability, leading to limited residence time in tissues. Even if CPPecp has been approved for the highly cellular permeability, short half-life is still a challenge for itself to become successful drug carriers due to multiple absorption, distribution, metabolism, and excretion (ADME) issues. In the present invention, strategies developed to improve peptide drugability through enhancing stability, reducing proteolysis, retaining permeability and increasing selective heparan sulfate binding activity are disclosed.
The above information disclosed in this section is only for enhancement of understanding of the background of the described technology and therefore it may contain information that does not form the prior art that is already known to a person of ordinary skill in the art.